Osel Inc. is striving to develop a novel approach to prevent vaginal HIV transmission. This approach involves genetically modifying non-pathogenic bacteria, resembling those found on mucosal surfaces, to produce molecules that have the capacity to bind, trap, and inactivate HIV. By colonizing the vaginal cavity with these bacteria, HIV will have the same affinity for the modified bacteria as the host cell. Binding of HIV to these modified bacteria should block subsequent transmission of virus to the host. As outlined in the present application, we propose to engineer a specific vaginally-derived strain of lactobacillus, L. crispatus, to express high affinity HIV binding proteins. Since L. crispatus is surrounded by a dense, proteinaceous surface component (S-layer), we propose to display a series of different HIV binding proteins on this S-layer, thus positioning these molecules to have ready access to HIV when introduced into the vaginal cavity. In these phase I studies, we will genetically modify these bacteria to display HIV binding ligands within various domains of the S-layer. We will subsequently demonstrate that these modified bacteria block HIV-infectivity in vitro. If completed successfully, these studies will position us to pursue in vivo testing of this product during Phase II investigations. PROPOSED COMMERCIAL APPLICATION: The novel approach proposed by Osel Inc. would find utility as a method to block HIV transmission. Since it is anticipated to be cost-effective, it can be used world-wide, including in under-developed countries. This product will be marketed as a vaginal suppository to be used on a weekly, or monthly, basis. It will be convenient to use and female-controlled. Importantly, this product concept is associated with an unmet medical meed and substantial commercial opportunity.